IgG-Switched CLL Has a Distinct Immunogenetic Signature from
the Common MD Variant: Ontogenetic Implications

J 2014

IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications

VARDI, A., A. AGATHANGELIDIS, L.A. SUTTON, M. CHATZOULI, L. SCARFO et. al.

Základní údaje

Originální název

IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications

Autoři

VARDI, A. (300 Řecko), A. AGATHANGELIDIS (380 Itálie), L.A. SUTTON (752 Švédsko), M. CHATZOULI (300 Řecko), L. SCARFO (380 Itálie), L. MANSOURI (752 Švédsko), V. DOUKA (300 Řecko), A. ANAGNOSTOPOULOS (300 Řecko), Nikos DARZENTAS (300 Řecko, garant, domácí), R. ROSENQUIST (752 Švédsko), P. GHIA (380 Itálie), C. BELESSI (300 Řecko) a K. STAMATOPOULOS (300 Řecko)

Vydání

Clinical Cancer Research, PHILADELPHIA, American Association for Cancer Research, 2014, 1078-0432

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 8.722

Kód RIV

RIV/00216224:14740/14:00078459

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1158/1078-0432.CCR-13-1993

UT WoS

000329918600008

Klíčová slova anglicky

CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL RECEPTOR; GENE MUTATIONAL STATUS; SOMATIC HYPERMUTATION; CLONAL EVOLUTION; UNMUTATED CLL; ANTIGEN; RECOMBINATION; ACTIVATION; EXPRESSION

Štítky

kontrola MP, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 2. 2015 14:09, Martina Prášilová

Anotace

V originále

Purpose: Immunoglobulin G-switched chronic lymphocytic leukemia (G-CLL) is a rare variant of CLL, whose origin and ontogenetic relationship to the common IgM/IgD (MD-CLL) variant remains undefined. Here, we sought for clues about the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires. Experimental Design: Using purpose-built bioinformatics methods, we performed detailed immunogenetic profiling of a multinational CLL cohort comprising 1,256 cases, of which 1,087 and 169 expressed IG mu/delta and gamma heavy chains, respectively. Results: G-CLL has a highly skewed IG gene repertoire that is distinct from MD-CLL, especially in terms of (i) overuse of the IGHV4-34 and IGHV4-39 genes and (ii) differential somatic hypermutation (SHM) load. Repertoire differences were also found when comparing subgroups with similar SHM status and were mainly attributed to the exclusive representation in G-CLL of two major subsets with quasi-identical (stereotyped) B-cell receptors. These subsets, namely #4 (IGHV4-34/IGKV2-30) and 8 (IGHV4-39/IGKV1(D)-39), were found to display sharply contrasting SHM and clinical behavior. Conclusions: G-CLL exhibits an overall distinct immunogenetic signature from MD-CLL, prompting speculations about distinct ontogenetic derivation and/or immune triggering. The reasons underlying the differential regulation of SHM among G-CLL cases remain to be elucidated. (C) 2013 AACR.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

EE2.3.20.0045, projekt VaV

Název: Podpora profesního růstu a mezinárodní integrace výzkumných týmů v oblasti molekulární medicíny

Citovat

VARDI, A., A. AGATHANGELIDIS, L.A. SUTTON, M. CHATZOULI, L. SCARFO, L. MANSOURI, V. DOUKA, A. ANAGNOSTOPOULOS, Nikos DARZENTAS, R. ROSENQUIST, P. GHIA, C. BELESSI a K. STAMATOPOULOS. IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications. Clinical Cancer Research. PHILADELPHIA: American Association for Cancer Research, 2014, roč. 20, č. 2, s. 323-330. ISSN 1078-0432. Dostupné z: https://dx.doi.org/10.1158/1078-0432.CCR-13-1993.

@article{1217014,
   author = {Vardi, A. and Agathangelidis, A. and Sutton, L.A. and Chatzouli, M. and Scarfo, L. and Mansouri, L. and Douka, V. and Anagnostopoulos, A. and Darzentas, Nikos and Rosenquist, R. and Ghia, P. and Belessi, C. and Stamatopoulos, K.},
   article_location = {PHILADELPHIA},
   article_number = {2},
   doi = {http://dx.doi.org/10.1158/1078-0432.CCR-13-1993},
   keywords = {CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL RECEPTOR; GENE MUTATIONAL STATUS; SOMATIC HYPERMUTATION; CLONAL EVOLUTION; UNMUTATED CLL; ANTIGEN; RECOMBINATION; ACTIVATION; EXPRESSION},
   language = {eng},
   issn = {1078-0432},
   journal = {Clinical Cancer Research},
   title = {IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications},
   url = {http://clincancerres.aacrjournals.org/content/20/2/323.long},
   volume = {20},
   year = {2014}
}

TY  - JOUR
ID  - 1217014
AU  - Vardi, A. - Agathangelidis, A. - Sutton, L.A. - Chatzouli, M. - Scarfo, L. - Mansouri, L. - Douka, V. - Anagnostopoulos, A. - Darzentas, Nikos - Rosenquist, R. - Ghia, P. - Belessi, C. - Stamatopoulos, K.
PY  - 2014
TI  - IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications
JF  - Clinical Cancer Research
VL  - 20
IS  - 2
SP  - 323-330
EP  - 323-330
PB  - American Association for Cancer Research
SN  - 10780432
KW  - CHRONIC LYMPHOCYTIC-LEUKEMIA
KW  - B-CELL RECEPTOR
KW  - GENE MUTATIONAL STATUS
KW  - SOMATIC HYPERMUTATION
KW  - CLONAL EVOLUTION
KW  - UNMUTATED CLL
KW  - ANTIGEN
KW  - RECOMBINATION
KW  - ACTIVATION
KW  - EXPRESSION
UR  - http://clincancerres.aacrjournals.org/content/20/2/323.long
L2  - http://clincancerres.aacrjournals.org/content/20/2/323.long
N2  - Purpose: Immunoglobulin G-switched chronic lymphocytic leukemia (G-CLL) is a rare variant of CLL, whose origin and ontogenetic relationship to the common IgM/IgD (MD-CLL) variant remains undefined. Here, we sought for clues about the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires. Experimental Design: Using purpose-built bioinformatics methods, we performed detailed immunogenetic profiling of a multinational CLL cohort comprising 1,256 cases, of which 1,087 and 169 expressed IG mu/delta and gamma heavy chains, respectively. Results: G-CLL has a highly skewed IG gene repertoire that is distinct from MD-CLL, especially in terms of (i) overuse of the IGHV4-34 and IGHV4-39 genes and (ii) differential somatic hypermutation (SHM) load. Repertoire differences were also found when comparing subgroups with similar SHM status and were mainly attributed to the exclusive representation in G-CLL of two major subsets with quasi-identical (stereotyped) B-cell receptors. These subsets, namely #4 (IGHV4-34/IGKV2-30) and 8 (IGHV4-39/IGKV1(D)-39), were found to display sharply contrasting SHM and clinical behavior. Conclusions: G-CLL exhibits an overall distinct immunogenetic signature from MD-CLL, prompting speculations about distinct ontogenetic derivation and/or immune triggering. The reasons underlying the differential regulation of SHM among G-CLL cases remain to be elucidated. (C) 2013 AACR.
ER  -

VARDI, A., A. AGATHANGELIDIS, L.A. SUTTON, M. CHATZOULI, L. SCARFO, L. MANSOURI, V. DOUKA, A. ANAGNOSTOPOULOS, Nikos DARZENTAS, R. ROSENQUIST, P. GHIA, C. BELESSI a K. STAMATOPOULOS. IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications. \textit{Clinical Cancer Research}. PHILADELPHIA: American Association for Cancer Research, 2014, roč.~20, č.~2, s.~323-330. ISSN~1078-0432. Dostupné z: https://dx.doi.org/10.1158/1078-0432.CCR-13-1993.

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